DESCRIPTION: (Applicant's Description) Little is known about individual differences in susceptibility to nicotine dependence among youth. While most adolescents experiment with tobacco, the majority do not go on to develop a pattern of habitual use and nicotine dependence. While both familial and biobehavioral factors are important in predicting cigarette use, little is known about; 1) the familial aggregation of smoking especially among adolescents and first degree relatives (parents and siblings); 2) the nicotine use and dependence phenotypes which are transmitted from parent to child; and 3) heritable biobehavioral substrates which may predispose toward nicotine dependence. Characteristics related to disruptive behavior disorders (e.g., attention deficit hyperactivity disorder, conduct disorder) and mood disorders (e.g. depression) are associated with smoking in both youth and adults. Maternal smoking during pregnancy increases the likelihood of youth smoking and young adult nicotine dependence, and is simultaneously associated with a variety of developmental and neurocognitive deficits (e.g., ADHD; conduct disorder) that may increase the likelihood of developing nicotine dependence by potentiating the reinforcing effects of nicotine. The aims of this proposal are to study associations between: (1) Adolescent comorbid disruptive behavioral disorders, mood disorders, and the progression of nicotine dependence; (2) Corresponding parental and sibling comorbid smoking, nicotine dependence, antisocial, ADHD, and mood disorders in relation to adolescents' progression of nicotine dependence; and (3) Effects of maternal smoking during pregnancy on incidence and trajectory of comorbid disruptive behavioral and mood disorders and nicotine dependence. Accordingly, 644 families (adolescents, siblings and parents) will be studied prospectively over 3 years to determine those factors which predict progression of nicotine dependence. This prospective family study will utilize both existing and new data gathered as part of the National Collaborative Perinatal Project (NCPP), whose New England cohort includes over 16,000 adults who have been followed since birth, whose early neurological, cognitive, and psychological functioning has been documented, and whose children are, on average, 14 years old, and will be 17 years old when the proposed study is complete. We propose to study comorbid disruptive behavioral and mood disorders in these children, their parents and siblings, and use this information to predict progression of nicotine dependence.